Large numbers of people, worldwide, say they do not want to be vaccinated against the SARS-CoV-2 virus, despite the deaths and the havoc it has caused. Mistrust of vaccines is not new, but the pandemic has shown how extensive it is. Asked for the reasons for their mistrust people commonly refer to a fear of side-effects. This paper discusses systems for reporting vaccine-related side effects and suggests they should be modified in order to promote greater public confidence.
Over the past 40 years growing numbers of parents have chosen not to fully immunize their children (1). It is a global phenomenon. As it became clear that this was happening an explanation, and with it a culprit, were sought and found. The consensus in public health was that anti-vaccination groups spreading misinformation through the internet were to blame (2). Looking for guidance online, parents often came across their messages, and consequently vaccination rates began to fall. Convinced their child had suffered vaccine damage, some American parents demanded financial compensation from the manufacturers (3). The result was that some pharmaceutical companies abandoned vaccine production entirely. There were fears that the nation’s vaccine supply was in jeopardy (4). In 1986, the United States Congress responded with the National Childhood Vaccine Injury Act. Its purpose was to cover vaccine manufacturers against potential damage claims. But it also included the requirement that any ‘adverse event’ following, and perhaps due to, vaccination should be reported to a central registry. We’ll return to this and other such registries.
It took longer for public health professionals to acknowledge that the activities of ‘anti-vaxxers’ alone could not adequately account for falling vaccination rates (5). Whilst very few people have strong anti-vaccination convictions, many more are doubtful about vaccination (6). Growing numbers of parents feel anxious and uncertain. Recognizing that the problem was one largely of confidence rather than of principle, a new term came into use: vaccine hesitancy (7).
The COVID-19 pandemic has shown how widespread vaccine hesitancy really is. Surveys in various countries have found 10, 20, and even 30% of people reluctant to be vaccinated against COVID-19, despite well over 2 million deaths worldwide.
When ‘vaccine hesitant’ people are questioned about their doubts, many say that they don’t trust vaccines (6). Specifically, they don’t trust individuals and institutions who insist that vaccines are perfectly safe. Vaccine doubters are worried by the possibility of vaccines causing adverse events.
What are vaccine-related ‘adverse events’?
Any health problem occurring after vaccination is potentially an “adverse event” due to the vaccine. The issue could of course be coincidental, or there could be a causal link between the vaccination and the symptoms. Demonstrating causality is key to establishing whether adverse reactions are due to a particular vaccine.
In the case of COVID-19 vaccines, mild flu-like symptoms are the most common side effects. During clinical trials, mild side effects were reported almost as frequently by people receiving the placebo as by those receiving the vaccine. This suggests that the process of vaccination itself is partly responsible for the reported side effects..When a large population is vaccinated, from a statistical point of view some people are likely to develop illnesses soon after vaccination. Since millions of people are being vaccinated against COVID-19 within a short timeframe, numerous reports of symptoms were to be expected. This does not mean that all these illnesses are to be considered adverse events due to the vaccine, even though some may be reported as such.
In early March 2021 fears of something more serious than a two-day flu as a consequence of COVID-19 vaccines emerged. A possible association between the AstraZeneca vaccine and thromboembolic symptoms was suggested, with many European countries pausing their roll-out of this vaccine. At the root of this situation were reports that about 40 people had developed blood clots after receiving the vaccine. Reviews by experts found very rare cases of blood clots (25 cases from over 20 million people vaccinated in Europe), for which “causal link with the vaccine is not proven, but is possible and deserves further analysis”. Initial suspension of the AstraZeneca vaccine was based more on political considerations than on scientific evidence, which was inconclusive. Governments wanted to demonstrate they were being extremely careful in protecting their citizens. People needed – and still need – reassurance. Was pausing vaccination the right way to reassure people? In a recent review of the cases of 86 patients who had developed blood clots, from more than 25 million who had received the vaccine, the European Medicines Agency concluded that this is indeed a vaccine related adverse event, albeit an extremely rare one. It stands by its earlier conclusion that the risk of side effects is greatly outweighed by the benefits of continuing to use the vaccine.
Vaccine pharmacovigilance: monitoring adverse events
Vaccine adverse events are monitored through national and transnational databases. In the US, the Vaccine Adverse Events Reporting System (VAERS), was established in 1990. Many other countries then followed suit. These databases are part of the wider field of pharmacovigilance, in which reports of suspected adverse reactions to pharmaceutical products are studied for possible causal links (8).
The different national databases are mostly managed by the organizations that regulate and approve new drugs and vaccines. For example, in Italy the vaccine pharmacovigilance system is organized and managed by the Italian Medicines Agency. In the Netherlands these activities are conducted by an ad hoc institute, LAREB, whilstIndia’s Federal government established a surveillance mechanism under the Universal Immunisation Programme more than a decade ago. It is called the Adverse Events Following Immunisation surveillance system, AEFI. It has a National Secretariat, whose network across the country is meant to identify and monitor anyone suffering from severe adverse symptoms, irrespective of whether these involve hospitalisation or not. In Australia adverse effects can be reported to the Therapeutic Goods Administration (TGA). The UK has a system called ’yellow card’, managed by the Medicines and Healthcare Products Regulatory Agency, MHRA. Through these systems, anyone can report an adverse event, either through a special website or in some cases through a downloadable app. As expected, most of the reported side effects tend to be due to direct reactions to the jab, such as a sore arm, headache, tiredness and fever, rather than to the vaccine itself. But despite all these national systems being in place, most people are unaware of their existence and do not know how to report adverse post-vaccination events.
How do these databases work?
The information pooled in these databases comes from reports, which in theory can be uploaded by anyone: patients, manufacturers and health professionals. These reports are categorized and statistically elaborated at the national level, as well as in a European system managed by the European Medicines Agency (EMA) and a worldwide system managed by the World Health Organization.
In order to report post-vaccination symptoms, a person has to regard the symptoms as in some way significant; they have to know about the reporting system and have access to it; and they have to think that reporting their symptoms is actually worth the effort, that it has some value. Since we were curious to understand how people make this assessment in practice, we conducted a small qualitative analysis by asking three friends in three different countries to tell us about their post-COVID-19 vaccination experiences and whether or not they had reported potential adverse events anywhere. Of note, two of the people we approached are sociologists with a long experience of studying health care and associated technologies, whilst the third one is a health professional.
A few hours after the first shot of the vaccine, person A (in the UK) experienced heavy flu-like symptoms. Shivering, sweating, headache and pain in his joints forced him to stay in bed. Despite his fatigue A. could hardly sleep. He felt bad for three days, and then slowly recovered. Even if these are unpleasant symptoms, they do not have long lasting invalidating consequences. As a medical sociologist, A. already knew about the Yellow cards scheme. Surprised by the adverse events, which were much worse than his brother’s, he soon learned that his symptoms were common reactions to the vaccine, albeit more prolonged than usual. A. did not report his symptoms to the Yellow card system until after our conversation.
D. is a health professional who also owns and manages an elderly care home in Italy. While the first dose went smoothly for all staff and residents, the second jab went well for everyone except him. He received the second shot in the morning and at around 8 pm he suddenly felt sick. He felt extremely tired, with articular pain and a headache. During the night he couldn’t sleep and had an intense stomachache. These symptoms lasted 24 hours and then vanished abruptly. D. did not report his experiences. Though vaguely aware of the existence of a reporting system, he didn’t know that anyone could report adverse events, where exactly, or how. Like A, D. too heard from others that his symptoms were similar to those experienced by others, though more severe. He wasn’t particularly worried.
R, in India, was vaccinated together with her husband. In a written response to our query, she told us that she didn’t know about any reporting system. “There are no clearly specified guidelines, as far as I know. But I could be wrong…they kept us there for observation for 30 minutes after the jab, and at the end of it we were asked if we felt anything was amiss. We felt fine and continued our day. My symptoms kicked in about 18 hours later. I got a fever, chills and a heavy and painful head and eyes, symptoms that went away after three days but which laid me low during that time. My husband felt nothing at all. I guess that if anything strange started to happen, or if the symptoms persisted for many days or worsened, I would have phoned the hospital where I got the shot to ask their advice. The person in charge had given us his mobile number”.
These three stories illustrate how informed people assess their post-vaccination experiences. Deciding whether they should be worried by their symptoms is a subjective and personal process, in which the experiences of others also play a role. For both A. and D., knowing about these experiences helped them make sense of their own. However, most people are not aware of how to report symptoms following vaccinations. Epidemiologists working in the pharmacovigilance field know their methodologies aren’t perfect. They acknowledge that “events that are not hypothesized to be drug related, “might be underreported, “unless the events are very severe.” They speculate as to whether a proactive system, in which people are questioned about their experiences, would be better than one that relies on voluntary reporting (9). Perhaps new approaches are required. Thus, Rebecca Chandler, at the Uppsala Center in Sweden, which monitors drug and vaccine safety, writes: “Traditional vaccine pharmacovigilance must evolve to support continued research for the purpose of improved assessments of causality that aligns with the progress in vaccine safety science” (10).
What should vaccine pharmacovigilance do?
How should data be collected? How can data collection be standardized across countries? Epidemiologists continuously debate methodological questions such as these. The way the various reporting systems work and the methodological discussions taking place are in pursuit of greater statistical reliability. However, statistical confidence does not translate directly into public confidence, as the recent experience with the AstraZeneca vaccine shows. Current debate seems exclusively focused on enhancing statistical confidence. How might adverse events reporting systems be modified so that they could contribute not only to epidemiologists’ confidence but to public confidence too?
Three London-based physicians have recently called “for monitoring of vaccine safety to occur out of the media limelight as sensationalist and exaggerated reporting will do irreparable damage to vaccine confidence”. We disagree. Secrecy promotes mistrust, not confidence. We suggest that transparency is essential for public confidence in vaccines to be enhanced. Systems for reporting adverse events following vaccination should therefore be widely known and easily accessible. People must trust them independently and seriously to investigate whatever post-vaccination symptoms they experience and report.
Vaccine hesitancy is having a real impact, especially in countries where large numbers of people have the option of being vaccinated (this is not the case in many developing countries). In May 2020 we suggested that clarity regarding responsibility in the event of side effects would be essential for public confidence, but to no avail. We hope this article will open a debate and will help to identify ways in which systems for reporting adverse events can become better known and fully trusted. This, we feel, can contribute to reducing vaccine hesitancy and rebuilding public confidence in vaccines.
Stuart Blume and Maurizia Mezza
References:
- Iacobucci G., “Child vaccination rates in England fall across the board, figures show” British Medical Journal, 2019.
- Gangarosa, E. J., et al., “Impact of anti-vaccine movements on pertussis control: The untold story’”, Lancet, 1998.
- Ridgway, D., “No-fault vaccine insurance: lessons from the National Vaccine Injury Compensation Program” Journal of Health Politics Policy and Law, 1999.
- Office of Technology Assessment Review of Federal Vaccine and Immunization Policies Washington DC: US Government Printing Office, 1979.
- Blume, S., “Anti-vaccination movements and their interpretations”, Social Science & Medicine, 2006.
- Karafillakis,E., and H J. Larson, “The benefit of the doubt or doubts over benefits? A systematic literature review of perceived risks of vaccines in European populations”, Vaccine, 2017.
- Dubé, E., et al, ” Vaccine hesitancy”, Human Vaccines & Immunotherapeutics, 2013.
- Chandler, R.E., “Modernising vaccine surveillance systems to improve detection of rare or poorly defined adverse events”, British Medical Journal, 2019.
- Huang, Y.L., et al., “A comparison of active adverse event surveillance systems worldwide”, Drug Safety, 2014.
- Chandler, R.E., “Safety concerns with HPV vaccines continue to linger: are current vaccine pharmacovigilance practices sufficient?” Drug Safety, 2017.
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